Closing out his discussion on the management of metastatic melanoma, expert oncologist Sajeve Thomas, MD, summarizes unmet needs and looks toward future evolutions in the treatment paradigm.
Sajeve S. Thomas, MD: Half the patients we treat upfront are going to have primary resistance, so we need to focus on that population, and we’re excited about TIL [tumor-infiltrating lymphocyte] and multiple other clinical trial options that we have with modulating agents to help the patients who are not going to respond, or maybe [to] respond better. Certainly, folks had a response and then over time now have acquired resistance. What do we do with those folks? Do we treat them the same way as somebody with primary resistance? I’m really excited about cellular therapy. As I said earlier, I’m really excited about intratumoral therapies. There are multiple trials looking at intratumoral and cell therapies in various forms and other IO [immunotherapy] therapies that are out there in targeting, again, the Holy Grail, the T cells, to turn them on. They target the gut microbiome, and target the tumor microenvironment with creating a more pro-inflammatory environment. These are all exciting options.
Certainly, patients not responding to PD-1 therapy should look into a clinical trial. The other unmet need is the folks with metastatic brain disease, but half those patients can respond to ipilimumab/nivolumab. If folks are symptomatic and requiring steroids, that might be a tough option again. There are some clinical trials looking at triple therapy, especially the BRAF-mutated BRAF MEK in combination with PD-1 versus ipi/nivo in this group of patients. [In] mucosal melanoma, another tough group of patients, I’m seeing some exciting responses with cell therapy. [With] acral melanoma, believe it or not, sometimes this subgroup is being excluded for some of the trials that we have, and so another population that may not respond as high as you expect with other types of cutaneous melanoma. I think we should maybe target that population a bit better as well. Maybe even think about more aggressive therapies upfront for the acral, mucosal subtypes. Certainly, uveal melanoma is the stepchild of all melanomas, a bit different than what we see with cutaneous and mucosal, but certainly we are excited about some trials that we have at our own institution of targeting uveal melanoma in a different way. The summary is clinical trials.
I think you’re going to see a lot of new things, and I kind of said it over and over. Here is intratumoral therapy and cell therapy, and also newer forms of cell therapy in terms of modifying the T cells or TIL therapy. I think those are probably the more exciting things. Also, the adjuvant therapy. With patients who have high-risk stage III right now, the standard cure for these patients is to give adjuvant PD-1 therapy. If they’re BRAF mutated, we can think about adjuvant BRAF MEK. I think it’ll be exciting to see data from studies, such as this ongoing study of doing PD-1 with LAG-3, versus PD-1. We’ll see what the result of that study looks like and other ways of giving therapy as well for that population.
Transcript edited for clarity.